Lack of a single protein could lead to lifelong viral infection

(Reuters)

The difference between a virus getting cleared out of the body or a virus staying in the body forever – think HIV or hepatitis C – may come down to a single protein, according to a new study.

The study also looked at immune system defects that occur as a consequence of missing or altered versions of the protein, pointing to a signaling pathway in the body that may be a useful target for treatment of persistent viral infections, which affect hundreds of millions of people worldwide.

The protein, known as toll-like receptor 7 (TLR7), is one of the body’s first defenses against invading viruses.  It exists inside the cell and is programmed to sense a virus once it has entered the cell.  The protein then alerts the immune system to the virus’s presence, triggering a response to fight off the virus.

When scientists from The Scripps Research Institute engineered mice without the protein, then subsequently infected them with a persistent virus, they found the mice were unable to clear the virus for the rest of their lives. Meanwhile, mice with intact versions of the protein were able to clear the infection within 60 to 90 days.

Furthermore, the absence of the protein caused a number of other defects in the immune environment of the engineered mice.

For example, the researchers found that even when they transplanted immune 'memory' cells, which learn how to fight off infections and lead to lifelong immunity, from mice with the protein to mice without the protein, the mice without the protein were still unable to fight off the infection.

The mice without the protein also had high levels of tired T cells, which are less functional and much less capable of fighting off infections than normal T cells, even when there are greater numbers tired T cells present.

According to study leader and Scripps Research professor Dr. Michael Oldstone, the research points to the need to examine TLR7 for abnormalities or defects in humans with persistent viruses.

“The defects you find would probably be generalized to the entire population,” Oldstone told FoxNews.com.  “If you know what the defects are, you can learn what it takes to eliminate or [make up] for them.”

The new research adds to previous work in determining all the factors that need to be addressed before finally developing treatments that can prevent or cure persistent infections like HIV and hepatitis C in humans, according to Oldstone.

“Scientists have [previously] identified the two molecules, interleukin-10 and programmed cell death protein 1, which negatively regulate the immune system, so it doesn’t work properly,” Oldstone said.  “Then you have what we found, which means there are other types of things that need to be taken into consideration.”

The study results were published Wednesday in the journal Cell Host & Microbe.